The rational design of bacterial toxin inhibitors


Clark, GC; Basak, AK; Titball, RW; (2007) The rational design of bacterial toxin inhibitors. Current computer-aided drug design, 3 (1). pp. 1-12. ISSN 1573-4099

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Abstract

Protein toxins play key roles in many infectious diseases of humans which are caused by bacteria. In some cases the toxin alone is directly responsible for the majority of the symptoms of the disease (e.g. tetanus, anthrax, diphtheria). In others the toxin is one of an arsenal of virulence factors which allow the bacterium to cause disease. Antibiotics are currently the mainstay for the treatment of bacterial infections. However, increasing levels of antibiotic resistance and the indiscreet nature of antibiotic therapy are limitations. Prior to the availability of antibiotics, antisera against toxins were often used to treat bacterial disease. Nowadays, animal-sourced products, such as antisera, are generally not acceptable for use in humans. Against the background there is an increasing interest in the development of low molecular weight inhibitors of toxins for the treatment of disease. For some toxins, like anthrax toxin, botulinum toxin and shigella toxin, low molecular weight inhibitors demonstrate proof of principle of this concept. For most other toxins the design and development of inhibitors is now a very real prospect; the crystal structures of many toxins are available, and in most cases the identity of the substrate or receptor is known. This article describes in detail the rational design of bacterial toxin inhibitors.

Item Type: Article
Keywords: antitoxin, toxin inhibitor, botulinum toxin, shiga-toxin, anthrax toxin, Neurotoxin type-b, shiga-like toxin, hemolytic-uremic syndrome, shock-syndrome toxin-1, anthrax lethal factor, pore-forming toxins, pseudomonas-aeruginosa infection, staphylococcus-aureus infection, perfringens alpha-toxin, low nanomolar affinity
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Pathogen Molecular Biology
Web of Science ID: 247933000001
URI: http://researchonline.lshtm.ac.uk/id/eprint/9221

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